BLOOD VOLUME & VENOUS RETURN IN THERMAL STRAIN

揭示解释等离子体体积的机制 随着培训而进行的扩展是 这份续签申请书。血浆体积膨胀提供了 维持适当的静脉回流，因此维持 热应激条件下的动脉血压。为了研究这些 在人类的机制中，我们已经开发出一种剧烈运动模型 在运动后24小时产生10.5%的血浆体积膨胀。我们 打算为运动大鼠开发一个类似的模型，使我们能够 探讨相关的细胞和器官系统机制。 我们的具体目标是：(1)完善我们的人体模型 频繁测血对血浆容量膨胀的研究 剧烈运动后72小时内尿量和尿液成分的变化 锻炼身体。利用这个模型，我们将检验以下假设：(I)A CP压力感受性反射敏感性降低先于血容量扩张， 从而允许将膨胀的体积保留在血管中 车厢。我们将比较血浆容量和CP压力反射敏感性 在从剧烈运动中恢复的过程中频繁地间隔时间来测试这一点。 (Ii)剧烈运动后血浆白蛋白含量开始升高(1-2小时) 运动起源于间质，随后的(24小时)抬高 血浆白蛋白含量增加是由于肝脏合成白蛋白增加所致 费率。我们将使用稳定同位素方法来测量 血浆中白蛋白合成速率和白蛋白分布 扩张期。(3)肾脏对游离水的清除减少 和溶质在紧随其后的等离子体体积膨胀期间 运动(最长72小时)。我们将确定是否减少用水量 而溶质清除是由于醛固酮和 抗利尿激素(AVP)。(四)强烈的运动刺激会导致 与条件相比，口渴增加，对Na+的适口性提高 在没有剧烈运动的情况下，血浆渗透压增加，因此 促进更快的补水。我们将检查口渴和 对不同方案中Na+的适口性。(2)发展动物 用于研究等离子体体积膨胀的模型。我们打算使用一个 运动大鼠模型，在别人示范的基础上 在跑步机上跑步后增加血浆容量。有了这种模式，我们将 检验以下假设：(I)以下血浆体积膨胀 剧烈运动在很大程度上是由白蛋白合成增加引起的。 以及它在维管室中的积聚。我们将衡量 直接合成白蛋白。(Ii)某些盐分和水分滞留 激素导致原位灌流肝脏白蛋白合成增加 准备工作。我们将测量恢复中的动物的白蛋白合成 在肝脏灌流期间进行剧烈运动，并给予适当剂量的 肾素、AVP和醛固酮，(III)促进白蛋白合成 剧烈运动是由于肝脏白蛋白信使核糖核酸增加。 翻译。我们将测量肝脏白蛋白mRNA的百分比 总信使核糖核酸，使用翻译分析，在不同时间之前和 在老鼠完成了一项高强度运动方案之后。

Uncovering the mechanisms accounting for the plasma volume expansion that occurs with training is the primary, long-term goal of this renewal application. Plasma volume expansion provides for the maintenance of an adequate venous return, and therefore maintenance of arterial blood pressure in conditions of thermal strain. To study these mechanisms in humans, we have developed an intense exercise model that produces a 10.5% expansion of plasma volume 24 h after exercise. We intend to develop an analogous model for the exercising rat, enabling us to investigate the relevant cellular and organ system mechanisms. Our specific aims are: (1) To refine our human model for the study of plasma volume expansion by making frequent measurements of blood and urine volume and constituent changes over 72 h following intense exercise. With this model, we will test the following hypotheses: (i) A reduction in CP baroreflex sensitivity precedes blood volume expansion, thereby allowing the expanded volume to be retained in the vascular compartment. We will compare plasma volume and CP baroreflex sensitivity at frequent intervals during recovery from intense exercise to test this. (ii) An initial (1-2 h) elevation in plasma albumin content after intense exercise is of interstitial origin and the subsequent (24 h) elevation in plasma albumin content is due to increased hepatic albumin synthetic rate. We will use stable isotopic methodology to measure changes in albumin synthetic rate and albumin distribution during the plasma volume expansion period. (iii) There is a reduced renal clearance of free water and solutes during the plasma volume expansion period following intense exercise (up to 72 h). We will determine whether the reduction in water and solute clearance is due to increased action of aldosterone and antidiuretic hormone (AVP). (iv) The intense exercise stimulus will cause increased thirst and improved palatability to Na+ compared to conditions in which plasma osmolality increases without intense exercise, thus promoting a more rapid rehydration. We will examine thirst and palatability to Na+ in different protocols. (2) To develop an animal model for the study of plasma volume expansion. We intend to use an exercising rat model, based upon the demonstrations of others that rats expand plasma volume after treadmill running. With this model, we will test the following hypotheses: (i) Plasma volume expansion following intense exercise is in large part caused by increased albumin synthesis and its accumulation in the vascular compartment. We will measure albumin synthesis directly. (ii) Certain of the salt and water retention hormones cause increased albumin synthesis in an in situ, perfused liver preparation. We will measure albumin synthesis in animals recovering from intense exercise during liver perfusion with appropriate doses of renin, AVP and aldosterone, (iii) Increased albumin synthesis following intense exercise is due ti) increased hepatic albumin mRNA available for translation. We will measure hepatic albumin mRNA as a percentage of total mRNA, using a translation assay, prior to and at various times after rats have completed an intense exercise protocol.